Advanced HIV disease and advanced age are both associated with impaired neurocognitive function. The emergent population of people living and now aging with HIV infection and being treated with potent antiretrovirals has little risk of developing classic HIV-related opportunistic illnesses. However, this population does appear to be at increased risk of conditions associated with aging, such as cardiovascular disease and frailty.

The authors of a recently published study [Goodkin K, Miller EN, Cox C, et al. Lancet HIV. 2017;4(9)] sought to evaluate whether HIV disease accelerates age-related neurocognitive decline. The authors analyzed a subset of data from the MACS (Multicenter AIDS Cohort Study) that included people with and without HIV infection, who had undergone repeated, extensive neurocognitive testing to assess functioning in five domains: information processing speed, episodic memory, executive function, motor function, and working memory. The researchers included medical and demographic data in their analysis to control for multiple potential confounders, such as education, income, alcohol use, other drug use, comorbid diseases, antiretroviral therapy era, HIV stage (using CDC staging
), and duration of infection since HIV seroconversion.

Advanced age (>50 years) and advanced HIV stage were each associated with lower neurocognitive scores. Increasing age was associated with lower scores across all domains. Participants with CDC Stage A or B HIV (asymptomatic or early symptomatic) had neurocognitive scores similar to those without HIV. However, those with Stage C HIV (AIDS) had lower scores for motor function and working memory. Furthermore, there was an interaction between aging and advanced HIV leading to a multiplicatively greater decline in motor function and episodic memory.

When the model included time since seroconversion, people living with Stage C HIV (AIDS) also had significantly lower scores on motor function and episodic memory and a greater decline in both with aging, when compared with those with less advanced HIV or those uninfected with HIV. The researchers described an anatomical correlate that may explain these motor function and episodic memory results: The basal ganglia and hippocampus are both affected by HIV, often with early involvement. Motor function depends on the basal ganglia, and the hippocampus is critical for episodic memory.

This study highlights the value of neurocognitive testing to evaluate potential cognitive decline in people living with HIV. Results can help to quantify the level of impairment and help guide diagnoses. The study results suggest that, in a patient with a history of advanced HIV infection, a finding of greater decline in motor function and episodic memory than in other domains is consistent with primary HIV-related brain disease. If other patterns of neurocognitive decline--in executive function, for example--are identified, then a non-HIV-related cause may be more likely and further evaluation may be warranted.

Questions still to be answered include: (1) What is the long-term effect of HIV infection on someone started on antiretroviral therapy soon after seroconversion who maintained an undetectable viral load long-term? (2) What is the effect of HIV infection among individuals >70 years of age? (3) What is the potential effect on neurocognitive performance over time of HIV medications that are neurotoxic or that have greater central nervous system penetration? I look forward to future publications from this and other groups to further explain the long-term neurocognitive implications of HIV infection and successful HIV treatment.

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